Chromosome movements that regulate tissue-specific gene expression

在2013财年，我们实现了以下目标： 第一章 使用高分辨率3D-FISH完成YY 1缺陷、YY 1敲除和CTCF敲除pro-B细胞中IgH基因座构象的研究。 结果证实了我们提出的pro-B细胞中IgH基因座结构模型的预测。 （二） 博士我们的常驻专家Tatiana Gerasimova与几位校外研究人员合作，将短探针FISH技术应用于其他相关生物系统。 在与埃默里大学的维克托科尔斯博士的合作中，我们发现ES细胞特异性基因的染色质构型是由计算研究预测的结构蛋白决定的。 在与Amy Kenter博士（伊利诺伊大学医学院）的合作中，我们发现3 280 kb的IgH基因座在活化的B细胞中经历了可诱导的循环，为类别转换重组做准备。 这种环的形成依赖于YY 1，如YY 1缺陷型天然B细胞的分析所示（与Michael Atchison博士（宾夕法尼亚大学）合作完成）。 第三章 用位点4突变小鼠启动研究，以观察活细胞中的IgH等位基因。

In FY13, we accomplished the following: 1) Completed studies of IgH locus conformation in YY1-deficient, YY1-knockdown and CTCF-knockdown pro-B cells using high-resolution 3D-FISH. The results substantiate the predictions of our proposed model for IgH locus architecture in pro-B cells. 2) Dr. Tatiana Gerasimova, our resident expert, collaborated with several extramural investigators to apply short-probe FISH technology to other relevant biological systems. In a collaboration with Dr. Victor Corces (Emory University), we showed that chromatin configuration of ES cell-specific genes was determined by structural proteins predicted from computational studies. In a collaboration with Dr. Amy Kenter (University of Illinois Medical School), we showed that the 3 280 kb of the IgH locus underwent inducible looping in activated B cells preparing for class switch recombination. This loop formation was dependent on YY1 as shown by analysis of YY1-deficient nature B cells (done in collaboration with Dr. Michael Atchison (University of Pennsylvania). 3) Initiated studies with Site 4 mutant mice to visualize IgH alleles in living cells.